How is AKT pathway activated?

Akt is activated downstream of vascular endothelial growth factor (VEGF) in endothelial cells in the lining of blood vessels, promoting survival and growth. Akt also contributes to angiogenesis by activating endothelial nitric oxide synthase (eNOS), which increases production of nitric oxide (NO).

Does AKT activate bad?

Akt phosphorylates BAD in vitro and in vivo, and blocks the BAD-induced death of primary neurons in a site-specific manner. These findings define a mechanism by which growth factors directly inactivate a critical component of the cell-intrinsic death machinery.

Does AKT translocate to nucleus?

Despite AKT action is known to function mainly in the cytoplasm, AKT has been reported to translocate to the nucleus. However, very little is known about the mechanism required for the nuclear import of AKT as well as its function in this cellular compartment.

Where does AKT come from?

AKT (now also called AKT1) was originally identified as the oncogene in the transforming retrovirus, AKT8. AKT8 was isolated from a spontaneous thymoma cell line derived from AKR mice by cocultivation with an indicator mink cell line.

How does PIP3 activate Akt?

PIP3 recruits AKT to the plasma membrane, allowing TORC2 to phosphorylate a conserved serine residue of AKT. Phosphorylation of this serine induces a conformation change in AKT, exposing a conserved threonine residue that is then phosphorylated by PDPK1 (PDK1).

Does Akt prevent apoptosis?

Akt inhibits apoptosis induced by microinjection of cytochrome c and lysates from cells expressing active Akt inhibit cytochrome c induced caspase activation in a cell-free assay while lysates from Bcl-2–expressing cells have no effect.

Does Akt inhibit bad?

Akt has recently been shown to phosphorylate and inactivate Bad in primary neurons and in vitro (8, 31). Indeed, in Rat1a cells, activated Akt was unable to efficiently inhibit apoptosis mediated by a mutant of Bad (Bad*) in which the two serine residues were converted to alanine (Fig. 6A).

Is AKT a nuclear protein?

Furthermore, we found that nuclear AKT was activated in MCF7E cells upon stimulation. The possibility that nuclear activated AKT was translocated from the cytoplasm was excluded through the generation of a chimeric AKT protein, in which a strong nuclear localization signal was fused to the C-terminal of AKT.

What regulates Akt?

Akt regulates critical cellular processes including cell survival and proliferation, glucose metabolism, cell migration, cancer progression and metastasis through phosphorylation of a variety of downstream targets.

Is Akt an oncogene?

AKT was first discovered in the 1970s as an oncogene transduced by the transforming retrovirus (AKT‐8), which was isolated from an AKR mouse thymoma cell line and first molecularly cloned in 1991.

How does PIP3 activate PDK1?

PIP3 formation is negatively regulated by the PTEN tumor suppressor protein, a phosphatase that dephosphorylates PIP3 and coverts it to PIP2. PIP3 recruits AKT and PDK1 to the plasma membrane, enabling the PDK1 to phosphorylate AKT on a conserved threonine residue.